Hypoxia-Inducible Factors in Physiology and Medicine

By G. Semenza. Cell, 2012

3,301 citations recorded by the source corpus.

Oxygen homeostasis represents an organizing principle for understanding metazoan evolution, development, physiology, and pathobiology. The hypoxia-inducible factors (HIFs) are transcriptional activators that function as master regulators of oxygen homeostasis in all metazoan species. Rapid progress is being made in elucidating homeostatic roles of HIFs in many physiological systems, determining pathological consequences of HIF dysregulation in chronic diseases, and investigating potential targeting of HIFs for therapeutic purposes.

Subfields: Cancer Research, Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/2a166fe7961f5035dca3ce1e8d1d6923ff6a6b16

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Citations in the corpus

Oxidative Stress in Cancer (2020, background): “Activation of HIF-1α increases expression of proangiogenic genes, such as that for vascular endothelial growth factor, which is associated with metastatic disease (Semenza, 2012).”
From Krebs to Clinic: Glutamine Metabolism to Cancer Therapy (2016, background): “BPTES inhibition of hGA(124-551), a truncated form of human kidneytype glutaminase.”
Cellular adaptation to hypoxia through HIFs and beyond (2020, background): “Together with Semenza (2012), this review provides an excellent outline of the regulation and importance of HIFs in physiology and diseases.”
Metformin inhibits mitochondrial complex I of cancer cells to reduce tumorigenesis (2014, background): “HIFs are involved in metabolic adaptation of tumor cells to hypoxia (Semenza, 2012).”
Characteristics and Significance of the Pre-metastatic Niche. (2016, background): “Other well-known hypoxic response target genes that have been linked to pre-metastatic niche formation include SDF-1a, TGF-b, MMP-2,MMP-9, and CXCR4 (Semenza, 2012).”
Transcriptional Regulation by Hypoxia Inducible Factors (2013, background): “…important for maintaining oxygen homeostasis, however, are HIF targets involved in autophagy, apoptosis, redox homeostasis, inflammation and immunity, stemness and self-renewal, and metastasis and invasion (Figure 2; (Chi et al., 2006; Mole et al., 2009; Semenza, 2012b; Wenger et al., 2005).”
ROS Function in Redox Signaling and Oxidative Stress (2014, background): “The resulting tissue hypoxia stabilizes the family of transcription factors termed hypoxia-inducible factors (HIFs) [60].”
Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions (2023, background): “The main mediators of transcriptional hypoxic responses are HIF-1α and HIF-2α, which induce gene transcription, leading to hypoxic responses, and are involved in the regulation of carcinogenesis as well as stromal responses.(210) HIF-1α has important functional roles in both innate and adaptive immu”
Fundamentals of cancer metabolism (2016, background): “Themetabolic adaptation to hypoxia is coordinated by HIF-1, which induces metabolic genes involved in increasing glycolytic flux (23).”
Osteoarthritis: pathogenic signaling pathways and therapeutic targets (2023, methodology): “The hydroxylated HIF-α protein is tagged by the pVHL (von HippelLindau) factors with polyubiquitin, and subsequently targeted for degradation.(277) When the cells are under hypoxic conditions, the activity of PHDs is inhibited, leading to impaired hydroxylation and accumulation of HIF-α proteins in ”
Mitochondrial reactive oxygen species and cancer (2014, background): “The pathway consists of three hypoxia-sensitive α subunits (HIF1α, HIF2α, and HIF3α) that, upon activation, heterodimerize with the constitutively expressed HIF1β and activate transcription from hypoxia-response elements (HREs) [44].”